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Gene and Protein Information ![]() |
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class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 466 | 8p21.2 | ADRA1A | adrenoceptor alpha 1A | |
Mouse | 7 | 466 | 14 D1 | Adra1a | adrenergic receptor, alpha 1a | |
Rat | 7 | 466 | 15p12 | Adra1a | adrenoceptor alpha 1A |
Database Links ![]() |
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Specialist databases | |
GPCRdb | ada1a_human (Hs), ada1a_mouse (Mm), ada1a_rat (Rn) |
Other databases | |
Alphafold | P35348 (Hs), P97718 (Mm), P43140 (Rn) |
ChEMBL Target | CHEMBL229 (Hs), CHEMBL2822 (Mm), CHEMBL319 (Rn) |
DrugBank Target | P35348 (Hs) |
Ensembl Gene | ENSG00000120907 (Hs), ENSMUSG00000045875 (Mm), ENSRNOG00000009522 (Rn) |
Entrez Gene | 148 (Hs), 11549 (Mm), 29412 (Rn) |
Human Protein Atlas | ENSG00000120907 (Hs) |
KEGG Gene | hsa:148 (Hs), mmu:11549 (Mm), rno:29412 (Rn) |
OMIM | 104221 (Hs) |
Pharos | P35348 (Hs) |
RefSeq Nucleotide | NM_000680 (Hs), NM_013461 (Mm), NM_017191 (Rn) |
RefSeq Protein | NP_000671 (Hs), NP_038489 (Mm), NP_058887 (Rn) |
UniProtKB | P35348 (Hs), P97718 (Mm), P43140 (Rn) |
Wikipedia | ADRA1A (Hs) |
Natural/Endogenous Ligands ![]() |
(-)-adrenaline |
(-)-noradrenaline |
Download all structure-activity data for this target as a CSV file
Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The first α1A-adrenoceptor to be cloned was the bovine homolog. No species significant differences in pharmacology have been identified. The approved drug oxymetazoline has been mapped to the primary targets α1A and α2A adrenoceptors as these have comparably the highest affinity interaction with the drug. This does not preclude clinically relevant activity at other adrenoceptors. |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific antagonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Compounds such as prazosin and RS-17053 show unexpectedly low potency in certain isolated tissue assays (e.g. canine prostate) [28]. This was postulated to result from a novel α1- adrenoceptor subtype (α1L). It is now thought that this may result from differences in α1A-adrenoceptor characteristics dependent on tissue or assay environment [17]. RS-100329 and Ro-70-0004 are both 50-fold selective for α1A-adrenoceptors over the α1B- and α1D-adrenoceptor subtypes [94]. Doxazosin is selective for α1-adrenoceptors. alfuzosin is an approved drug which is an antagonist of several α1-adrenoceptors. Compounds designated as "partial inverse agonists" [54] are listed as neutral antagonists. |
Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Allosteric Modulator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
Whilst diazepam reduces the potency of phenylephrine to stimulate the IP response in Rat-1 fibroblasts expressing the α1A-AR, no change in the maximum IP response is observed. In contrast, the maximum IP response to clonidine (a weak partial agonist at α1A-AR) is increased by diazepam, midazolam and lorazepam, suggesting that the ability to detect allosteric potentiation is a function of both the intrinsic activity of the α1-AR agonist and the activity of the proposed modulator [90]. Data published by Williams et al. (2018) show that diazepam is not a direct allosteric modulator of α1-adrenoceptors [93], but is able to modulate receptor activity via inhibition of phosphodiesterase 4. Amiloride analogs will increase the dissociation rate of prazosin from the α1A-adrenoceptor [25]. Possible allosteric inhibition has been shown with ρ-TIA, a member of the ρ-conopeptide class of toxins derived from cone snails. ρ-TIA acts as an α1-adrenoceptor antagonist and is able to inhibit the norepinephrine-evoked increases in cytosolic-free calcium concentration and contractility. N-terminally truncated ρ-TIA analogues are less active than the full-length peptide. Upon deletion of the fourth residue of full-length ρ-TIA (in the form of the analog TIA5-19), antagonist activity is observed at 65% compared to the response observed in full length ρ-TIA. |
Primary Transduction Mechanisms ![]() |
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Transducer | Effector/Response |
Gq/G11 family |
Phospholipase C stimulation Calcium channel Other - See Comments |
Comments:
The α1A-adrenoceptor is coupled to calcium release and inositol phosphate production more efficiently than the other subtypes. The α1A-adrenoceptor is coupled to activation and translocation of Snapin and the TRPC6 channel to the plasma membrane and subsequent increase in Calcium entry and contractility. |
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References: 25,54 |
Secondary Transduction Mechanisms ![]() |
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Transducer | Effector/Response |
G12/G13 family |
Phospholipase A2 stimulation Phospholipase D stimulation Other - See Comments |
Comments:
α1-adrenoceptors (all subtypes) can also activate protein kinase C, mitogen activated protein kinases. G13 coupling observed in transfected CHO cells to regulate arachidonic acid release. PKCzeta coupling to phospholipase D observed in transfected rat-1 fibroblasts. |
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References: 25,38,54,63 |
Tissue Distribution ![]() |
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Expression Datasets ![]() |
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Functional Assays ![]() |
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Physiological Functions ![]() |
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Physiological Consequences of Altering Gene Expression ![]() |
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Xenobiotics Influencing Gene Expression ![]() |
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Phenotypes, Alleles and Disease Models ![]() |
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Gene Expression and Pathophysiology ![]() |
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Biologically Significant Variants ![]() |
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1. Amirahmadi F, Turnbull L, Du XJ, Graham RM, Woodcock EA. (2008) Heightened alpha1A-adrenergic receptor activity suppresses ischaemia/reperfusion-induced Ins(1,4,5)P3 generation in the mouse heart: a comparison with ischaemic preconditioning. Clin Sci, 114 (2): 157-64. [PMID:17696883]
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